Mitochondria with tubular cristae Nucleus •Fig. 38.9 Ultrastructure of a Steroidogenic Cell. Notetheabundanceoflipiddroplets,smoothendoplasmicreticulum,andmitochondriawithtubularcristae.(FromKierszenbaumAL.Histology and Cell Biology: An Introduction to Pathology. 2nded.Philadelphia:Mosby;2007.) level of secretion of the preformed hormone. A clinical implication of this mode of secretion is that high levels of steroid hormone precursors are easily released into blood when a steroidogenic enzyme within a given pathway is inactive or absent. The ultrastructure of steroidogenic cells is distinct from proteinand catecholamine-secreting cells. Steroidogenic enzymes reside within the inner mitochondrial membrane or the membrane of the smooth endoplasmic reticulum. Thus steroidogenic cells typically contain extensive mitochondria and smooth endoplasmic reticulum (
Fig. 38.9 ). These cells also contain lipid droplets, which represent a store of cholesterol esters.
An important feature of steroidogenesis is that steroid hormones often undergo further modifications (apart from those involved in deactivation and excretion) after their release from the original steroidogenic cell. For example, estrogen synthesis by the ovary and placenta requires at least two cell types to complete the conversion of cholesterol to estrogen. This means that one cell secretes a precursor and a second cell converts the precursor to estrogen. There is also considerable peripheral conversion of active steroid hormones. For example, the testes secrete little estrogen. However, adipose, muscle, and other tissues express the enzyme for converting testosterone (a potent androgen) to estradiol-17β (a potent estrogen). Thus the overall production of a particular steroid hormone is equivalent to the sum of the secretion of this steroid hormone from a steroidogenic cell type and peripheral conversion of other steroids to the particular steroid hormone (
Fig. 38.10 ). Peripheral conversion can produce (1) a more active but similar class of hormone (e.g., conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D); (2) a less active hormone that can be reversibly activated by another tissue (e.g., conversion of cortisol to cortisone in the kidneys, followed by conversion of cortisone to cortisol in abdominal adipose tissue); or (3) a different class of hormone (e.g., conversion of testosterone to estrogen). Peripheral conversion of steroids plays an important role in several endocrine disorders (see
Because of their nonpolar nature, steroid hormones are not readily soluble in blood. Therefore, steroid hormones circulate bound to transport proteins, including albumin, but also the specific transport proteins sex hormone– binding globulin and corticosteroid-binding globulin (see the section “
Transport of Hormones in the Circulation ”). Excretion of hormones from the body typically involves inactivating modifications, followed by glucuronide or sulfate conjugation in the liver, which is often coupled to biliary excretion. These modifications also increase the water solubility of the steroid and decrease its affinity for transport proteins, thereby allowing the inactivated steroid hormone to be excreted by the kidneys. Steroid compounds are absorbed fairly readily in the gastrointestinal tract and may therefore be administered orally.
Thyroid hormones are iodothyronines (Fig. 38.11 ) that are made by the coupling of iodinated tyrosine residues through an ether linkage. Their specificity is determined by the thyronine structure, as well as by where the thyronine is iodinated. Thyroid hormones cross cell membranes by •Fig. 38.10 Peripheralconversionofsteroidhormones.